The Effects of Cyclooxygenase Isozyme Inhibition onIncisional Wound Healing in Mouse Skin Karin Müller-Decker, Wolfgang Hirschner, Friedrich Marks, Gerhard Fürstenberger Journal of Investigative Dermatology Volume 119, Issue 5, Pages 1189-1195 (November 2002) DOI: 10.1046/j.1523-1747.2002.19501.x Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions
Figure 1 Gross appearance and progress of wound healing on back skin of mice fed control diet or diet supplemented with 500 p.p.m. valdecoxib or 64 p.p.m. SC-560. Photographs were taken 7 and 28 d after full thickness skin incisions were made. Journal of Investigative Dermatology 2002 119, 1189-1195DOI: (10.1046/j.1523-1747.2002.19501.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions
Figure 2 Kinetics of re-epithelialization and proliferation in full-thickness incisional skin wounds. Mice were fed control diet (A,B,G,H) or diet containing 500 p.p.m.valdecoxib (C,D,I,J) or 64 p.p.m.SC-560 (E,F,K,L) and analyzed 2 d (G–L), 3 d (A,C,E), and 7 d (B,D,F) after surgery. Specimens were stained with anti-COX-2 antibodies (A–F) or anti-Ki-67 antibodies (G–L). The wound edges are marked with arrows (G,I,K). Epidermis (e), granulation tissue (g), and eschar (es). Original magnification: × 630 (A–F, insert H), × 160 (G–L). (M) Kinetics of proliferation in interfollicular wound epidermis. Ki-67-immunopositive cells were counted in the wound center and the immediate neighboring fields. Values represent mean±SD (**p < 0.005, ***p < 0.0005) according to Student's t test, n=6 sections or 24 microscopic fields (original magnification×160)/group and time point. Journal of Investigative Dermatology 2002 119, 1189-1195DOI: (10.1046/j.1523-1747.2002.19501.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions
Figure 3 Localization of COX isozymes in incisional wounds by immunohistochemistry with goat anti-COX-1 (A–D) and goat anti-COX-2 (E–H) antibodies. Wound specimens were collected from control animals at various time points: 24 h (A,E,C,G), 7 d (D,H), and 28 d (B,F). Note COX-1 expression in suprabasal cells of interfollicular epidermis (A), dendritic cells (A, insert), endothelial cells (C), and macrophages (D). Note COX-2 expression in basal as well as suprabasal interfollicular keratinocytes (E), the outer root sheath of hair follicles and sebaceous gland epithelium (F), dendritic cells (E, insert), endothelial cells (G), as well as macrophages (H). Original magnification:×630. Journal of Investigative Dermatology 2002 119, 1189-1195DOI: (10.1046/j.1523-1747.2002.19501.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions
Figure 4 Localization of CD31-positive vessels in incisional wounds from animals fed control diet or diet supplemented with valdecoxib or SC-560. Wound specimens were collected 7 d postsurgery from animals fed control diet (A,A*), valdecoxib diet (B,B*), or SC-560 diet (C,C*), and processed for immunohistochemistry using rat anti-CD31 antibody. Original magnification: ×100 (A–C), × 630 (A*–C*). (D) Vessel density as function of time after incision. Microvessel density was determined in the wound centers as shown under A–C by counting CD31-immunopositive endothelial clusters. Values represent mean ± SD (**p < 0.05), according to Student's t test, n = 6 sections or 12 microscopic fields/group and time point. Journal of Investigative Dermatology 2002 119, 1189-1195DOI: (10.1046/j.1523-1747.2002.19501.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions
Figure 5 Collagen deposition in incisional wounds and tensile strength after treatment with COX inhibitors. Wound specimens collected 14 d postsurgery from animals fed control diet (A,A*), valdecoxib diet (B,B*), or SC-560 diet (C,C*) were stained using the Masson's trichrome procedure. Original magnification:×100 (A–C),×630 (A*–C*). Measurement of tensile strength of wounded skin was done by means of a tensiometer (D). Values represent mean±SD (n=25 stripes with five animals per group and time point). Indo, indomethacin. Journal of Investigative Dermatology 2002 119, 1189-1195DOI: (10.1046/j.1523-1747.2002.19501.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions